Feedback Loop Control of Neuromodulation Device

ABSTRACT

A method of controlling a neural stimulus, the neural stimulus being defined by at least one stimulus intensity parameter. The method comprises generating a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue, measuring a response of the tissue, evoked by the stimulus current, determining a forward adjustment parameter as a function of the stimulus intensity parameter, determining a feedback parameter derived from the measured response and the forward adjustment parameter and adjusting the stimulus intensity parameter according to the feedback parameter.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Stage Patent Application of PCT Patent Application No. PCT/AU2021/050993 filed on Aug. 27, 2021 which claims priority from Australian Provisional Patent Application No. 2020903091 filed on Aug. 28, 2020 and Australian Provisional Patent Application No. 2020903095 filed on Aug. 28, 2020, the contents of which are incorporated herein by reference in their entirety.

TECHNICAL FIELD

The present invention relates to controlling a neural response to a stimulus, and in particular relates to measurement of a compound action potential by using one or more electrodes implanted near a neural pathway, in order to provide feedback to control subsequently applied stimuli.

BACKGROUND

There is a range of situations in which it is desirable to apply neural stimuli in order to give rise to a compound action potential (CAP) in a tissue. For example, neuromodulation is used to treat a variety of disorders including chronic pain, Parkinson's disease, and migraine. A neuromodulation system applies an electrical pulse to tissue in order to generate a therapeutic effect. When used to relieve chronic pain, the electrical pulse is applied to the dorsal column (DC) of the spinal cord. Such a system typically comprises an implanted electrical pulse generator, and a power source such as a battery that may be rechargeable by transcutaneous inductive transfer. An electrode array is connected to the pulse generator, and is positioned in the dorsal epidural space above the dorsal column. The electrode array applies an electrical pulse to the dorsal column, which causes the depolarisation of neurons, and generation of propagating action potentials. This stimulates the nerve fibres and, as a result, inhibits the transmission of pain from that segment in the spinal cord to the brain. The electrode array applies stimuli continuously to sustain the pain relief effects. Neuromodulation may also be used to stimulate efferent fibres, for example to induce motor functions.

In general, the electrical stimulus generated in a neuromodulation system triggers a neural action potential which then has either an inhibitory or excitatory effect. Inhibitory effects can be used to modulate an undesired process such as the transmission of pain, or to cause a desired effect such as the contraction of a muscle.

The action potentials generated among a large number of fibres sum to form an electrically evoked compound action potential (ECAP). Accordingly, an ECAP is the sum of responses from a large number of single fibre action potentials. The ECAP recorded is the result of a large number of different fibres depolarising. The ECAP generated from the firing of a group of similar fibres is measured as a positive peak potential, then a negative peak, followed by a second positive peak. This is caused by the region of activation passing a recording electrode as the action potentials propagate along the individual fibres.

For effective and comfortable operation, it is desirable to maintain an electrical stimulus above a recruitment threshold, below which the electrical stimulus will fail to recruit any neural response and the patient will be unable to perceive an effect. It is also desirable to maintain an electrical stimulus which is below a comfort threshold, above which uncomfortable or painful percepts arise due to increasing recruitment of Aδ fibres, which are thinly myelinated sensory nerve fibres associated with acute pain, cold and pressure sensation. The comfort threshold is also known as the comfort stimulation intensity threshold.

The stimuli can be delivered within a therapeutic range (above the recruitment threshold and below the comfort threshold) by adjusting the applied stimulus based on a feedback signal. The feedback signal is based on a measured ECAP signal, detected by an electrode connected to the nerve fibres upstream of the stimulating electrode. Based on the ECAP signal, the applied stimulus can be adjusted to maintain the nerve stimulus within the therapeutic range. A method for achieving this is disclosed in U.S. Pat. Nos. 9,381,356 B2, and 10,500,399 B2 the contents of which is hereby incorporated.

The task of maintaining appropriate stimulus levels is made more difficult by electrode migration and/or postural changes of the implant recipient (patient), either of which can significantly alter the neural recruitment arising from a given stimulus, depending on whether the stimulus is applied before or after the change in electrode position or patient posture. Postural changes alone can cause a comfortable and effective stimulus regime to become either ineffectual or painful. Furthermore, it is often desirable to maintain stimulation at, or close to, a target stimulation level, within a therapeutic range.

Accordingly, it is desirable to provide a neural stimulation device that can maintain stimulation at, or close to, a target stimulation level, even in the event of electrode movement and/or postural changes of the patient.

Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.

Throughout this specification the word ‘comprise’, or variations such as ‘comprises’ or ‘comprising’, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

SUMMARY

There is provided a method of controlling a neural stimulus, the neural stimulus being defined by at least one stimulus intensity parameter. The method comprises generating a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue, measuring a response of the tissue, evoked by the stimulus current, determining a forward adjustment parameter as a function of the stimulus intensity parameter, determining a feedback parameter derived from the measured response and the forward adjustment parameter and adjusting the stimulus intensity parameter according to the feedback parameter.

In one embodiment, the forward adjustment parameter is non-zero when the stimulus intensity parameter is non-zero.

In one embodiment, the method further comprises determining a target response level, wherein determining a feedback parameter comprises, adjusting the target response level in accordance with the forward adjustment parameter to produce an adjusted target response level, and deriving the feedback parameter from a difference between the measured response and the adjusted target response level.

In one embodiment, determining a feedback parameter comprises adjusting the measured response according to the forward adjustment parameter to produce an adjusted response.

In one embodiment, the function of the stimulus intensity parameter is a forward adjustment function, wherein the forward adjustment function defines a monotonically increasing relationship between the forward adjustment parameter and the stimulus intensity parameter.

In one embodiment, the method further comprises determining a change in an impedance level of the tissue, adjusting a gradient of the forward adjustment function based on the change the impedance level.

In one embodiment, adjusting the gradient of the forward adjustment function comprises in response to an increase in the impedance level, reducing the gradient of the forward adjustment function, and in response to a decrease in the impedance level, increasing the gradient of the forward adjustment function.

In one embodiment, the feedback parameter is derived according to the difference between a target stimulus intensity level and the adjusted response.

In one embodiment, the method further comprises determining an adjusted target stimulus intensity level based on the target stimulus intensity level and the forward adjustment function.

In one embodiment, the method further comprises adjusting the forward adjustment function to increase a difference between the adjusted target stimulus intensity level and a comfort stimulus intensity threshold.

In one embodiment, the method further comprises determining an artefact compensation component based on an artefact component of the measured response of the tissue, and adjusting the measured response based on the artefact compensation component.

In one embodiment, the method further comprises determining the artefact component as a function of the stimulus intensity parameter.

In one embodiment, adjusting the measured response based on the artefact compensation component comprises adjusting the forward adjustment function based on the artefact compensation component.

In one embodiment, adjusting the stimulus intensity parameter according to the feedback parameter derived from the measured response comprises, in response to the measured response being greater than a target value, reducing the stimulus intensity parameter in accordance with a reduction rate, and, in response to the measured response being less than the target value, increasing the stimulus intensity parameter in accordance with a growth rate, wherein a magnitude of the reduction rate is not equal to a magnitude of the growth rate.

There is further provided an implantable device for controllably applying a neural stimulus defined by at least one stimulus intensity parameter. The device comprises one or more stimulus electrodes to deliver stimulus to a tissue to evoke a compound action potential response of the tissue, a stimulator for controlling the one or more stimulus electrodes in accordance with the at least one stimulus intensity parameter, measurement circuitry for measuring the evoked compound action potential response of the tissue, and a control unit configured to, generate the stimulus intensity parameter, measure the response of the tissue, evoked by the stimulus current, determine a forward adjustment parameter as a function of the stimulus intensity parameter, determine a feedback parameter derived from the measured response and the forward adjustment parameter, and adjust the stimulus intensity parameter according to the feedback parameter.

There is further provided a method of controlling a neural stimulus, the neural stimulus being defined by at least one stimulus intensity parameter. The method comprises generating a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue, measuring a response of the tissue, evoked by the stimulus current, determining an artefact compensation component as a function of the stimulus intensity parameter and indicative of an artefact component of the measured response, and adjusting the stimulus intensity parameter according to a feedback parameter derived from the measured response and the artefact compensation component.

In one embodiment, the method further comprises adjusting the measured response based on the artefact compensation component, to produce an adjusted measured response, and wherein, adjusting the stimulus intensity parameter comprises adjusting the stimulus intensity parameter according to a feedback parameter derived from the adjusted measured response and the artefact compensation component.

There is further provided, a method of controlling a neural stimulus, the neural stimulus being defined by at least one stimulus intensity parameter. The method comprises generating a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue, measuring a response of the tissue evoked by the stimulus current, in response to the measured response being greater than a target value, reducing the stimulus intensity parameter in accordance with a reduction rate, and in response to the measured response being less than the target value, increasing the stimulus intensity parameter in accordance with a growth rate, wherein a magnitude of the reduction rate is not equal to a magnitude of the growth rate.

In one embodiment, the method further comprises determining the reduction rate based on a duration of time for which the measured response is greater than the target value.

There is further provided a method of controlling a neural stimulus, the neural stimulus being defined by at least one stimulus intensity parameter. The method comprises generating a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue, measuring a response of the tissue, evoked by the stimulus current, determining a position of a set point of the measured response relative to a threshold, and adjusting the stimulus intensity parameter according to a feedback parameter derived from the measured response and the position of the set point relative to the threshold.

In one embodiment, determining the position of the set point, comprises, in response to the measured response being greater than the threshold, determining that the set point is in a supra-threshold region, and, in response to the measured response being less than the threshold, determining that the set point is in a sub-threshold region.

In one embodiment, adjusting the stimulus intensity parameter comprises, in response to the set point being in the supra-threshold region, adjusting the stimulus intensity parameter in accordance with a first adjustment rate, and in response to the set point being in the sub-threshold region, adjusting the stimulus intensity parameter in accordance with a second adjustment rate, which is different to the first adjustment rate.

In one embodiment, the method further comprises determining the position of a target stimulus intensity level relative to the threshold, wherein determining the position of the target stimulus intensity level relative to the threshold, comprises, in response to the target stimulus intensity level being greater than the threshold, determining that the position of the target stimulus intensity level is in a supra-threshold region, and, in response to the target stimulus intensity level being less than the threshold, determining that the position of the target stimulus intensity level is in a sub-threshold region.

In one embodiment, the method further comprises configuring the first adjustment rate according to the position of the target stimulus intensity level and the position of the set point, and configuring the second adjustment rate according to the position of the target stimulus intensity level and the position of the set point.

In one embodiment, the method further comprises adjusting the measured response according to a forward adjustment parameter determined as a function of the stimulus intensity parameter, to produce an adjusted measured response.

In one embodiment, the method further comprises configuring the forward adjustment parameter according to the set point of the adjusted measured response.

In one embodiment, the method further comprises configuring the forward adjustment parameter according to the set point of the adjusted measured response and a target stimulus intensity level.

In one embodiment, the threshold is a threshold above which the response may be measured reliably.

There is further provided an implantable device for controllably applying a neural stimulus defined by at least one stimulus intensity parameter. The device comprises one or more stimulus electrodes to deliver stimulus to a tissue to evoke a compound action potential response of the tissue, a stimulator for controlling the one or more stimulus electrodes in accordance with the at least one stimulus intensity parameter, measurement circuitry for measuring the evoked compound action potential response of the tissue, and a control unit configured. The control unit is configured to generate the stimulus intensity parameter, measure the response of the tissue, evoked by the stimulus current, determine a position of a set point of the measured response relative to a threshold, and adjust the stimulus intensity parameter according to a feedback parameter derived from the measured response and the position of the set point relative to the threshold.

BRIEF DESCRIPTION OF DRAWINGS

The invention will now be described with reference to the accompanying drawings, in which:

FIG. 1 schematically illustrates an implanted spinal cord stimulator in a patient, according to an embodiment;

FIG. 2 is a block diagram of an implanted stimulator, according to an embodiment;

FIG. 3 is a system schematic illustrating elements of a feedback loop, for maintaining neural stimulation at a desired level, according to an embodiment;

FIG. 4 is a graph illustrating a profile of a measured response signal, according to an embodiment;

FIG. 5 is a graph illustrating a profile of an adjusted response signal, according to an embodiment;

FIG. 6 is a system schematic illustrating elements a feedback loop, for maintaining neural stimulation at a desired level, according to an embodiment;

FIG. 7 is a graph illustrating the linear approximations of three profiles of three measured response signals, corresponding to three different postures of a patient, according to an embodiment;

FIG. 8 is a graph illustrating the profile of linear approximations of artefact components of a measured response signal, according to an embodiment;

FIG. 9 is a graph illustrating an profile of a measured response signal incorporating artefact compensation, according to an embodiment;

FIG. 10 is a system schematic illustrating elements a feedback loop incorporating artefact compensation, for maintaining neural stimulation at a desired level, according to an embodiment;

FIG. 11 is a system schematic illustrating elements of a feedback loop incorporating artefact compensation and a forward adjustment parameter, for maintaining neural stimulation at a desired level, according to an embodiment;

FIG. 12 is a graph illustrating dual gain rates associated with an profile of a response signal, for one posture of the patient, according to an embodiment;

FIG. 13 is a system schematic illustrating elements of a feedback loop incorporating dual gain rates, for maintaining neural stimulation at a desired level, according to an embodiment;

FIG. 14 is a graph illustrating operational states through which a stimulation system passes during posture changes of a patient, according to an embodiment;

FIG. 15 is a system schematic illustrating elements of a feedback loop incorporating dual gain rates and a forward adjustment parameter, for maintaining neural stimulation at a desired level, according to an embodiment;

FIG. 16 is a graph illustrating the regions of a profile of a response signal, according to an embodiment;

FIG. 17 is a graph illustrating supra-threshold set point of the system on an profile of a response signal, according to an embodiment;

FIG. 18 is a graph illustrating adjustment of profiles of a response signal by forward adjustment functions, according to an embodiment;

FIG. 19 illustrates a method of controlling a neural stimulus as described with reference to FIGS. 5 and 6 , according to an embodiment;

FIG. 20 illustrates a method of controlling a neural stimulus as described with reference to FIGS. 10 and 11 , according to an embodiment;

FIG. 21 illustrates a method of controlling a neural stimulus as described with reference to FIGS. 12 and 13 , according to an embodiment; and

FIG. 22 illustrates a method of controlling a neural stimulus as described with reference to FIGS. 15, 16, 17 and 18 , according to an embodiment.

DESCRIPTION OF EMBODIMENTS FIG. 1—Implanted Spinal Cord Stimulator

FIG. 1 schematically illustrates an implanted spinal cord stimulator in a patient 108, according to an embodiment. The stimulator comprises an electronics module 110 implanted at a suitable location. In one embodiment, the electronics module 100 is implanted in the patient's lower abdominal area or posterior superior gluteal region. In other embodiments, the electronics module 110 is implanted in other locations, such as a flank or sub-clavicular. The stimulator further comprises an electrode assembly 150 implanted within the epidural space and connected to the module 110 by a suitable lead. The stimulator further comprises an energy storage device 104 and a telemetry module 114. The energy storage device 104 may be any suitable energy storage device such as a battery or capacitor. Telemetry module 114 transfers power and/or data between an external device 102 and other modules of device 110. For example, the energy storage device 104 may receive power from charger associated with the external device 102. The telemetry module 114 may utilise any suitable type of transcutaneous communication 106 such as infrared (IR) and electromagnetic including capacitive and inductive transfer, to communicate with the external device 102.

FIG. 2—Neurostimulator Block Diagram

FIG. 2 is a block diagram of the implanted electronics module 110, according to an embodiment. Module controller 216 has an associated memory 218 storing patient settings 220, control programs 222 and the like. Controller 216 controls a pulse generator 224 to generate stimuli, such as current pulses, in accordance with the patient settings 220 and control programs 222. Electrode selection module 226 switches the generated pulses to the appropriate electrode(s) of electrode array 150, for delivery of the current pulse to the tissue surrounding the selected electrode. Measurement circuitry 228 is configured to capture measurements of neural responses sensed at sense electrode(s) of the electrode array as selected by electrode selection module 226.

Stimuli Amplitude in Therapeutic Range

For effective and comfortable operation of an implantable neuromodulation device, it is desirable to maintain stimuli amplitude within a therapeutic range. A stimulus current within a therapeutic range evokes an ECAP value that is above a recruitment threshold and below a comfort threshold. A neural modulation device can adjust the applied stimulus current based on a feedback signal that is determined in light of the measured value, to keep the evoked response within this therapeutic range, and approximate to a target stimulation level. For example, the neural modulation device may calculate an error between a target value (also called a target stimulus intensity level) and a measured ECAP value and adjust the applied stimulus to reduce the error as much as possible, such as by adding the weighted error to the present stimulus intensity parameter. A neural modulation device that operates by adjusting the applied stimulus based on a measured value is said to be operating in closed loop mode and will also be referred to as a closed loop neural stimulus (CLNS) device.

Summary of a CLNS Feedback Loop

A closed loop neural stimulus (CLNS) device comprises a stimulator which takes a stimulus intensity parameter and coverts it into a neural stimulus. The stimulus intensity parameter defines a stimulation pattern which produces an electrical pulse on stimulation electrodes. The stimulation pattern may define a stimulus current, a pulse width, alternating phase on/off, number of phases, number of stimulus electrode poles (bipolar, tripolar etc.), stimulus electrode position, stimulus to measurement distance and stimulus rate. The stimulation output by the stimulator has a summary value, usually the stimulus current, which is controlled by the feedback loop.

In an example CLNS system, the patient or clinician sets a target value at a desired stimulation level and the CLNS performs proportional-integral-differential (PID) control. In some examples, the differential contribution is disregarded and the CLNS system uses a first order integrating feedback loop. A clinician adjusts the gain value (proportional weight) K, to compensate for patient sensitivity (gradient of ECAP activation plot or profile). The stimulator produces stimulus in accordance with a stimulus intensity parameter, which produces an evoked ECAP response in the patient. The evoked response is detected and measured by the CLNS and compared to the target value.

The measured value, and its deviation from the target value, is used by the feedback loop to determine possible adjustments to the stimulus current to maintain an ECAP value at a given state to allow patients to receive consistent comfortable and therapeutic stimulation.

FIG. 3—Closed Loop Pathway

FIG. 3 is a system schematic illustrating elements and inputs of a closed feedback loop, for maintaining neural recruitment at a target value, according to an embodiment. The system 300 comprises a stimulator 312 which takes a stimulus intensity parameter (also known as a stimulus current value) s, and coverts it, in accordance with a set of stimulus parameters, to an electrical pulse on the stimulation electrodes (not shown). According to one embodiment, the stimulus parameters comprise alternating phase on/off, the number of phases, the number of stimulus electrode poles (bipolar, tripolar etc.), pulse width, stimulus electrode position, stimulus to measurement distance, stimulus rate. The stimulus output by the stimulator 312 thus has a summary value m, usually the pulse amplitude.

The stimulus crosses from the electrodes to the spinal cord 316; however, the neural recruitment arising from this is affected mechanical changes, including posture changes, walking, breathing, heartbeat and so on. Mechanical changes may cause impedance changes, or changes in the distance and orientation of the nerve fibres. The stimulus also generates an evoked response y 332, which may be approximated by the equation y=P(m−T) where T is the stimulus threshold and P is the gradient of the response function. Various sources of noise n may add to the evoked response y before the response is measured, including (a) artefact 314, which is dependent on both stimulus current and posture; (b) electrical noise from external sources such as 50 Hz mains power; (c) electrical disturbances produced by the body such as neural responses evoked not by the device but by other causes such as peripheral sensory input, EGG, EMG; and (d) electrical noise from amplifiers 318.

The value of the evoked response provides a measure of the recruitment of the fibres being stimulated. The greater the stimulus, the more recruitment and larger the evoked response. An evoked response typically has a maximum value in the range of microvolts, whereas the applied stimulus to evoke the response is typically several volts.

Detector

The evoked response 332 is amplified by the signal amplifier 318 and then measured by the detector 320. The detector 320 outputs a measured response, d 328. The comparator 324 compares the measured response 328 to the target value (also known as a target stimulus intensity level) to produce an error value, e. The error value, e, is input into the feedback loop controller 310.

The comparator 324 compares the value of the measured response signal to the target value as set by the target ECAP controller 304 and provides an indication of the difference between the value of the measured response signal and the target value to the feedback controller 310. This difference is the error value, e.

Feedback Controller

The feedback controller 310 calculates an adjusted stimulus intensity parameter, s, (which indicates the stimulus current) with the aim of achieving a measured response equal to the target value. Accordingly, the feedback controller 310 adjusts the stimulus intensity parameter, s, to minimise the error value, e. In a one embodiment, the controller 310 utilises a first order integrating feedback loop function, using a gain controller 336 and an integrator 338, in order to provide suitable feedback control to maintain constant paraesthesia/recruitment and/or maintain ECAP at a predefined level to allow patients to receive consistent comfortable and therapeutic stimulation.

A target value is input to the comparator 324 via the target ECAP controller 304. In one embodiment, the target ECAP controller 304 provides an indication of a specific target value. In another embodiment, the target ECAP controller 304 provides an indication to increase or to decrease the present target value. The target ECAP controller 304 may comprise an input into the neural stimulus device, via which the patient or clinician can input a target value, or indication thereof. The target ECAP controller 304 may comprise memory in which the target value is stored, and provided to the comparator 324.

A clinical settings controller 302 provides clinical parameters to the system, including the gain rate for the gain controller 336 and the stimulation parameters for the stimulator 312. The clinical settings controller 302 can be configured to adjust the gain value, K, of the gain controller 336 to compensate for patient sensitivity. The clinical settings controller 302 may comprise an input into the neural stimulus device, via which the patient or clinician can adjust the clinical settings. The clinical settings controller 302 may comprise memory, in which the clinical settings are stored, and are provided to components of the system 300.

Two clocks (not shown) are used in this embodiment, being a stimulus clock operating at ˜60 Hz and a sample clock for measuring the evoked response operating at ˜10 KHz. As the detector is linear, only the stimulus clock affects the dynamics of the feedback loop 300. On the next stimulus clock cycle, the stimulator 312 outputs stimulus parameters in accordance with the adjusted stimulus current value. Accordingly, there is a delay of one stimulus clock cycle before the stimulus parameters are updated in light of the error value e.

FIG. 4—ECAP Threshold

An profile graph is a linear approximation of the relationship between a range of stimulus current values and the measured (or evoked) ECAP values resulting from the stimulus current.

FIG. 4 illustrates an profile 402 for a measured response signal, d, as output from the detector 320, according to one embodiment, for a range of stimulus current values and one posture of the patient. The evoked CAP response signal, as input into the detector 320, has a noise component. Accordingly, there is an ECAP threshold 404, indicated in terms of a stimulus current, below which the detector 320 cannot reliably distinguish the evoked ECAP value from the noise component. The ECAP threshold 404 is a point on the profile of a measured response signal, and may be referred to in terms of the ECAP value at the ECAP threshold, or the stimulus current value at the ECAP threshold. Defining the threshold in terms of the stimulus current has the advantage that the stimulus current is directly available to the controller, while the ECAP value is subject to a noisy measurement. In one embodiment, the ECAP threshold is defined as the stimulus current at which the signal to noise ratio (SNR) of the measured response signal is greater than a SNR threshold. In one embodiment, the SNR threshold is 1. In one embodiment, the ECAP threshold is pre-set by clinical settings. In one embodiment, the ECAP threshold is experimentally set.

For values below the ECAP threshold 404, the detector 320 outputs an value of zero via the measured response signal, d 328.

Profile 402 has a zero ECAP value from the point at which the stimulus current is zero, until the ECAP threshold 404. From the ECAP threshold 404, the profile 402 has a positive gradient indicating a linear relationship between stimulus current and the value of the measured response signal, d.

The measured response signal may also comprise an artefact component. An artefact component is not present in the embodiment illustrated in FIG. 4 , but will be described in relation to other embodiments, below. If an artefact is adding a positive component to the measured response, the ECAP value corresponding to the ECAP threshold will have a positive value. Similarly, if an artefact is adding a negative component to the measured response, the ECAP value corresponding to the ECAP threshold will have a negative value.

Perception Threshold

FIG. 4 also illustrates an example comfort threshold 408, above which the patient experiences uncomfortable or painful stimulation, and an example perception threshold 410. The perception threshold corresponds to an ECAP value that is perceivable by the patient. There are a number of factors which can influence the position of the perception threshold with respect to the stimulus current, including the posture of the patient.

Perception threshold 410 may correspond to a stimulus current that is greater than the stimulus current corresponding to the ECAP threshold 404, as illustrated in FIG. 4 , if the patient does not perceive low levels of neural activation. Conversely, the perception threshold may correspond to a stimulus current that is less than the stimulus current corresponding to the ECAP threshold 404, if the patient has a high perception sensitively to low levels of neural activation.

Furthermore, the stimulus current corresponding to the ECAP threshold 404 may be greater than the stimulus current corresponding to the perception threshold if the signal to noise ratio of the evoked response signal, input into the detector 320, is low.

Maintaining Stability at Low Target ECAPs

Some patients find it beneficial to run the system at the stimulus current equal to or below the ECAP threshold 404.

The feedback system illustrated in FIG. 3 detects an ECAP value of the measured response, d 328, that is greater than the noise level of the system. It can be difficult for a feedback controller to stabilise the feedback loop at a target value that is at or below the ECAP threshold, because the low signal to noise ratio at low ECAP values can result in an unreliable value for the measured response output from the detector.

Additionally, or alternatively, it can be difficult for a feedback controller to stabilise the feedback loop at a target value that is at or below the ECAP threshold, because the horizontal component of the profile from the origin to the ECAP threshold means that there is a range of stimulus current values which result in a measured response value of zero.

In an attempt to stabilise the feedback loop at or below the ECAP threshold, the feedback loop may switch on and off in an unstable state, resulting in an uncomfortable, or ineffective stimulation for the patient.

Additionally, when the patient changes posture quickly, the stimulation could cause an overstimulation, in the form of an ECAP value greater than the target value, or greater than the comfort threshold 408. Limiting the increase of the ECAP during sudden movements, even when the target value is near or under the ECAP threshold can be beneficial.

Furthermore, an artefact can cause an offset in the measured response signal such that the value of the measured response is negative at the patient's preferred stimulation setting. This can lead to meta-stability in the feedback loop, as the feedback controller 310 increases the stimulus current to raise the detected ECAP value, but the resulting measured value exceeds the patient's target value. Meta-stability can be avoided by clipping negative ECAP values within the detector before outputting the measured response, d, but then some patients are unable to run the stimulation as low as they would like or need.

Accordingly, it is desirable to allow for a neural stimulation device to accommodate the preference of some patients to stabilise the stimulation at low target stimulus intensity levels.

FIG. 5—Improved System Transfer Function

FIG. 5 illustrates a profile 502 for the value of a measured response signal, d, as output from the detector 320, for one posture of the patient, according to one embodiment. In this embodiment, the signal profile 502 has a zero value from the origin 510, at which the stimulus current is zero, until the ECAP threshold 504. From the ECAP threshold 504, the signal profile 502 has a positive gradient representing the approximately linear relationship between the stimulus current and the value.

Profile 506 is a linear approximation of the profile of a forward adjustment function, according to an embodiment. The profile 506 defines a forward adjustment function, which in the embodiment illustrated in FIG. 5 , is a linear function with respect to the stimulus current. The profile 506 of the forward adjustment function has a positive gradient from the origin 510. In one embodiment, a forward adjustment function with the profile 506 is combined with a measured response signal with the profile 502 to produce an adjusted response signal with the adjusted profile 512.

In one embodiment, the measured response signal is combined with a forward adjustment parameter that has a profile defined by the forward adjustment function. In another embodiment, the magnitude of the measured response signal at a particular stimulus current value, is increased by a forward adjustment parameter that is determined by the forward adjustment function applied at the same stimulus current value.

In one embodiment, the forward adjustment function is defined as ƒ=c.s, where ƒ is the forward adjustment parameter, c is a positive constant and s is the stimulus current value. The positive constant, c, defines the gradient of the forward adjustment function. In one embodiment, the positive constant, c, is configurable by the feedback controller. In one embodiment, the feedback controller determines the adjusted measured response d′ by adding the forward adjustment parameter to the measured response, in the form d′=d+ƒ.

The adjusted profile 512 has a positive gradient from the origin 510 to the point 524 at which the adjusted response signal meets the ECAP threshold 504. Accordingly, the value, of the adjusted profile 512, at stimulus currents below the ECAP threshold 504, is not horizontal along the x-axis, but rather it is monotonically increasing from the origin 510 to the ECAP threshold 504. That is, the value at the ECAP threshold of the adjusted profile 512 has a positive non-zero value at point 524.

The raising of the profile 502 by the forward adjustment function, allows the feedback controller to target a set point at a non-zero value, when the stimulus current is at or below the ECAP threshold 504.

The feedback controller adjusts the target value, according to the forward adjustment function, to calculate an adjusted target value 514. The feedback controller controls the feedback loop to stabilise the feedback loop at the adjusted target value 514.

In one embodiment, the adjusted target value is equal to the target value, as selected by the patient or selected in accordance with the clinical settings, increased by the value of the forward adjustment function 506 at the same stimulus current level. For example, if the target value is value 520 on profile 502, the feedback controller will set the adjusted value to value 522 on the adjusted profile 512.

In one embodiment, the feedback controller configures the forward adjustment function to an adjusted target value that is small compared to the comfort threshold 516, reducing the risk that the value of the evoked ECAP exceeds the comfort threshold 516.

Advantageously, adjusting the profile of the measured response signal according to a monotonically increasing function from the origin 510 to the ECAP threshold 504 provides a range 518 of positive values, which can be used by the feedback controller as the target value, for stabilising the feedback loop below the ECAP threshold 504.

In some embodiments, the feedback controller selects the gradient of the forward adjustment function to ensure that the value of the adjusted response signal, d′, at the patient's target value, is sufficiently raised above the noise level of the system to allow for accurate detection. For example, if the patient desires stimulation below the ECAP threshold, and the measured response signal comprises 2 μV of amplifier noise, the feedback controller selects the gradient of the forward adjustment function by raising the value of the adjusted response signal, d′, at the patient's target value, by 10 μV to reduce the effect of the amplifier noise.

FIG. 6 —Feedback Loop with Forward Adjustment Parameter

FIG. 6 illustrates a feedback loop 600 of a neural stimulation system, according to an embodiment. The feedback loop 600 comprises a target ECAP controller 604. In one embodiment, the target ECAP controller 604 comprises an input via which the patient or clinician can input a target value, or indication thereof. The target controller 604 may comprise memory in which the target value is stored, and provided to the comparator 620.

The feedback loop 600 further comprises a feedback controller 630 configured to adjust the stimulus current, s, to achieve or maintain the evoked response at the target value. With similarity to the feedback controller 310, illustrated in FIG. 3 , the feedback controller 630 utilises a first order integrating feedback loop function, comprising a gain controller 606 and an integrator 608, in order to determine suitable adjustments to the stimulus current, s, to achieve or maintain the evoked response at the target value.

The feedback controller 630 further comprises a forward adjustment parameter generator 612, which generates a forward adjustment parameter, ƒ 628. The signal combiner 624 combines the forward adjustment parameter, ƒ 628, with the measured response signal, d, to produce an adjusted response signal, d′ 634.

The comparator 620 compares the value of the adjusted response signal, d′ 634, to the target value (as provided by the target ECAP controller 604). The comparator 620 may be a subtraction operation or addition with negated input, and produces an error value, e, indicative of the difference between the value of the adjusted measured response, d′, and the target value. Based on the error value, e, the feedback controller adjusts the stimulus current, s, with the aim of achieving an adjusted measured response with an value equal to the target value.

The feedback controller 630 then maintains the stimulus current, s, effectively running at a constant current unless (a) the error value, e, indicates that the value of the adjusted response, d′ 634, deviates from the target value, or (b) the target value is changed by the target ECAP controller 604.

FIG. 7—Posture Changes

FIG. 7 illustrates the variation in the gradients of the profiles of the response signal with changing posture of the patient. As noted above, a change in posture of the patient may change the impedance level of the electrode-tissue interface, resulting in a different value profile of the response signal. While the profiles for only three postures, 702, 704 and 706, are shown in FIG. 7 , the profile for any given posture can lie between or outside the profiles shown, on a continuously varying basis depending on posture, with the profile moving at unpredictable times whenever the patient moves or changes posture.

In one embodiment, as the patient's posture changes, the stimulus current at ECAP threshold changes, as indicated by the ECAP thresholds 708, 710 and 712. Additionally, as the patient's posture changes, the gradient of the response profile also changes, as indicated by the gradients of profiles 702, 704 and 706.

As illustrated in FIG. 7 , if the patient moves from a position associated with profile 704 to a posture associated with profile 702, the gradient of the profile increases. Accordingly, the measured response will have a higher value for the same stimulus current level. In this case, the value of the measured response signal, when the patient is the posture associated with profile 702, may exceed the target value, it is desirable for the feedback controller to quickly reduce the stimulus current so that the value of the measured response falls back down to the target value.

In one embodiment, the feedback controller 630 adjusts gradient of the forward adjustment function (exemplified by profile 506 in FIG. 5 ) based on posture changes of the patient. Such an adjustment allows the feedback controller to maintain the gradient of the response signal profile within a preferred gradient range according to the sensitivity levels of the patient.

In one embodiment, the feedback controller 630 reduces the gradient of the forward adjustment function if the patient moves into a posture with a steeper response signal profile gradient. Conversely, the feedback controller increases the gradient of the forward adjustment function if the patient moves into a posture with a shallower response signal profile gradient. As the feedback controller 630 adjusts the forward adjustment function, the feedback controller 630 adjusts the adjusted target value 514 to compensate for the adjustment of the forward adjustment function.

FIG. 8—Artefacts

In some embodiments, a signal comprising an artefact component is generated within the neural tissue. The profile of the artefact component may be dependent on the stimulus current and the posture of the patient. In general, artefacts are signals detected by the electrodes that are not generated by the neural tissue. So artefacts are not part of the evoked CAP response. Instead, artefacts are measurements of the stimulation pulses themselves after they are applied to the neural tissue. Depending on the implementation of the stimulation device, these artefacts can cause an error in the ECAP measurements as they are difficult to distinguish from the evoked CAP response.

FIG. 8 illustrates profiles of example artefact components generated in response to a neural stimulus signal with the profile 806. In one embodiment, the artefact component has a voltage or amplitude profile which is approximately linear with respect to the stimulus current. The artefact component may have a negative gradient, as illustrated by profile 814, or a positive gradient, as illustrated by profile 812. The gradient of the gradient of the artefact profile may depend on the posture of the patient.

When an artefact component is present, the measured response signal output by the detector 618 is a combination of the artefact component and the evoked response signal. Accordingly, the signal output by the detector 618 will be a combination of a signal that is proportional to the stimulus current and a signal that is proportional to ECAP.

FIG. 9—ECAP Affected by Artefact

FIG. 9 illustrates the profiles of measured response signals 528 output by the detector 618 for situations in which the artefacts 812 and 814 are each, separately, combined with the evoked response signal 806, according to an embodiment. Profile 916 illustrates the profile of measured response signal, d 632, as output by the detector 618, when artefact 812 is present. The presence of artefact 812 raises the profile, such that there is a positive value at the ECAP threshold 908.

Profile 914 illustrates the profile of measured response, d 632, as output by the detector 618, when artefact 814 is present. When the artefact has a negative gradient, the activation plot slopes downward such that there is a negative value at the ECAP threshold 908. In this situation, the feedback loop can be bistable, which means that there are two stimulus current values, 910 and 912, that can produce a zero-valued measured response, d 632, as output from the detector 618. This can lead to meta-stability in the ECAP feedback loop as controlled by the feedback controller 630.

Meta-stability can be avoided by clipping negative values in the detector output, but then some patients are unable to run stimulation as low as they would like or need to achieve therapeutic benefit.

FIG. 10—Artefact Compensation Component to Forward Adjustment Function

FIG. 10 is a graph illustrating compensation of a negative artefact by a forward adjustment function, according to an embodiment. Profile 1006 is an example of the profile of an evoked response signal. Profile 1012 is the ECAP value profile of an example negative artefact which, when present in the system, combines with the profile 1006 of the evoked response signal to produce a measured response signal 632 with the profile 1014, as output by the detector 618.

In order to achieve an adjusted response signal, d′ 634, which has a profile that is monotonically increasing from the origin 1010, the feedback controller determines a forward adjustment parameter which comprises an artefact compensation component 1016, as well as a forward adjustment component 1018. The artefact compensation component 1016 negates the effect of the artefact 1012, and the forward adjustment component 1018 adjusts the profile so that it is monotonically increasing from the origin.

Combiner 624 of the feedback controller 630 combines the forward adjustment parameter with the measured response signal, which has profile 1014, to produce an adjusted response signal 634 with profile 1020.

FIG. 11 —Improved Loop with Artefact Compensation

FIG. 11 illustrates a feedback loop 1100 in which the feedback controller 1130 applies an artefact compensation component 1132 to the forward adjustment parameter ƒ 1128 to compensate for an artefact, a. The artefact compensation component 1132, is proportional to the stimulus signal s, and is of opposite sign and equivalent magnitude to the determined artefact, a. Accordingly, the artefact compensation component 1132 negates the effect of the artefact in the measured response, d, and the adjusted response 1134 represents the measured response without the artefact component.

In one embodiment, the artefact compensation component 1132 includes a fixed offset to compensate for a component of the artefact which is constant rather than being current dependent. In such an embodiment, the artefact compensation component 1132 is of the form ƒ=s·K_(a)+y, where y is the artefact when the stimulus current is 0 mA.

Dual Gain Rates

The gain rate, K₁ 606, defines the rate at which the stimulus current, s, is increased or decreased by the feedback controller 630 as the feedback controller seeks to achieve a zero-valued error, e output from the comparator 620. The gain rate K₁ 606 may be expressed as a percentage of the value of the adjusted or measured response signals, 632, 634. Alternatively, the gain rate K₁ 606 may be expressed as a multiplier of the value of the adjusted or measured response signals, 632, 634. The negation of the gain rate K₁, which may be called the loss rate ⁻K₁, is used by the feedback controller 630 to decrease the stimulus current, s.

Depending on a patient's therapeutic needs it may be advantageous to configure the feedback controller such that the gain rate differs in magnitude from the loss rate. For example, if the target value is close to the comfort threshold for a patient, it may be desirable to increases the stimulus current slowly up to the target value to reduce the risk of overshooting the target value. Furthermore, it may be desirable to decrease the stimulus current quickly if the stimulus current exceeds the target value. In another example, if the target value is close to the patient's perception threshold, it may be desirable to increase the stimulus current quickly if it falls below the target value, but decrease the stimulus current at a slower rate if the measured value rises above the target value.

In one embodiment, the clinical settings controller 1302 configures the feedback controller with indications of the locations of the perception threshold and comfort threshold on the ECAP response profile, for each of one or more postures of the patient.

In one embodiment, the feedback controller increases the stimulus current in accordance with a gain rate K₁, and decreases the stimulus current in accordance with a loss rate K₂ that is different in magnitude to the gain rate K₁. In one embodiment, the gain rate and/or the loss rate are configurable via the clinical settings controller 602.

FIG. 12—Dual Gain Example

FIG. 12 illustrates the profile 1202 of a measured response signal, as output from a detector, for one posture of a patient, according to an embodiment. The value of a measured response signal, d, will fall along the profile 1202, depending upon the stimulus current used to evoke the ECAP response. The feedback controller sets the target value 1204 to an target stimulus intensity level according to parameters set by the patient or the clinical settings.

The comparator 524 compares the value of the measured response signal, d, to the target value 1204 to provide an indication of the difference in value to the feedback controller 510.

If the value of the measured response signal, d, is below the target value 1204, for example, the measured value is at point 1208, the feedback controller increases the stimulus current at a rate set by gain rate K₁. The gain rate may also be determined as a function of the duration of the time for which the measured value was below the target. This function may be determined with the integrator 608. In some embodiments, the gain rate K₁ is determined as a function of the difference between the value of the measured (or adjusted) response signal and the target value. For example, the feedback controller 630 may increase the gain rate if the value of the measured (or adjusted) response signal is far below the target value.

If the value of the measured response signal exceeds the target value, for example, the measured value is at point 1206, then the feedback controller reduces the stimulus current at a rate determined by loss rate K₂. The reduction rate (or loss rate) may also be determined as a function of the duration of the time for which the measured value exceeds the target. This function may be determined with the integrator. In some embodiments, the loss rate K₂ is determined as a function of the difference between the value of the measured (or adjusted) response signal and the target value.

In one embodiment, the target value 1204, the gain rate K₁ and the loss rate K₂ are adjusted by a clinician. The target value can be set at or below the patient's maximum comfort threshold 1216.

FIG. 13—Dual Gain Pathway

FIG. 13 illustrates a feedback loop 1300 of a neural stimulation system, according to an embodiment. The feedback loop 1300 does not comprise a forward adjustment parameter generator. That is, this feedback loop 1300 does not adjust the measured response signal in accordance with a forward adjustment function.

The evoked response signal is detected by the detector 1318 and output to the comparator 1324, as measured response signal, d 1332. The comparator 1324 compares the value of the measured response signal to the target value set by the target controller 1304 and provides an indication of the difference, as error value e, to the feedback controller 1330. The feedback controller 1330 comprises a gain unit 1306 to increase the stimulus current in accordance with the gain rate K₁ if the difference is positive, as determined by the rectifier 1321, i.e. the ECAP value is less than the target ECAP value. If the difference is negative, i.e. the ECAP value is greater than the target ECAP value, the rectifier 1321 does not pass the difference along, and instead the stimulus current reduces to bring the ECAP value back to the target ECAP value at a rate set by a loss rate K₂ of the reduction unit 1320 included in the integrator 1308.

In one embodiment, the gain rate K1 and the loss rate K2 are set and configured by the clinical settings controller 1302. In one embodiment, the gain rate K1 and the loss rate K2 can by adjusted by the feedback controller 1330, based on the state of the system 1300, or the target value provided by the target ECAP controller 1304.

FIG. 14—System States

FIG. 14 shows the states a feedback loop system will follow, under normal operation, according to an embodiment. More specifically, FIG. 14 illustrates three example profiles, for the value of a measured response signal, for three postures. Profile 1402 is an example profile when the patient is in a supine posture, profile 1404 is an example profile when the patient is in a standing posture, and profile 1406 is an example profile when the patient is in a sitting posture.

In the example illustrated in FIG. 14 , the system has been set, by the patient or the clinician, to the target value 1408 in standing posture. The patient is at set point 1412. As the patient changes posture from standing to sitting, the value of the measured response decreases to point 1410. As the patient remains in the sitting posture, the feedback controller will increase the stimulus current to move the system along the sitting profile 1406, back to the target value 1408, ending at set point 1411.

When the patient is in the standing posture, and the system is at the target value, at position 1412, if the patient moves to a supine posture, then the value of the measured response increases sharply, up to the ECAP limit 1414. Then the feedback controller rapidly decreases the stimulus current to reach the set point 1413. This keeps the value at, or below, the ECAP limit 1414, and prevents the value reaching the comfort threshold 1416.

FIG. 15 —Dual Gain with Forward Adjustment Function

FIG. 15 illustrates a feedback loop 1500 of a neural stimulation system, according to an embodiment. Feedback loop 1500 comprises a feedback controller 1530 configured to provide a stimulus current reduction 1520 in accordance with loss term K₂, and stimulus current gain 1506 in accordance with gain term K₁. Feedback controller 1500 is further configured to provide adjustment of the measured response signal via a forward adjustment parameter generator 1512.

Accordingly, the feedback controller 1530, of the embodiment illustrated in FIG. 15 , comprises dual gain control of the stimulus current, and a forward adjustment parameter generator 1520 to adjust the profile of the measured response signal 1532.

FIG. 16—Two Regions of Operation

FIG. 16 is a graph illustrating a piecewise linear approximation of a profile 1602 for a measured response signal, d, according to an embodiment. The profile 1602 has an ECAP threshold at the stimulus current level 1604. The value at the ECAP threshold is a positive value at ECAP level 1606.

The profile 1602 comprises at least two domains of operation, namely a sub ECAP threshold (sub-threshold) region 1608 and a supra ECAP threshold (supra-threshold) region 1610.

For some embodiments, it may be advantageous to consider that the profile 1602 comprises more than two domains of operation, namely a sub ECAP threshold (sub-threshold) region 1608, a supra ECAP threshold region 1620 and a supra perception threshold region 1630. The supra perception threshold region 1630 extends from the perception threshold to the comfort threshold. A supra comfort threshold region 1640 represents the region of profile 1602 which extends above the comfort threshold. Above the comfort threshold, the patient may experience uncomfortable or painful stimulation. Accordingly, it is not typically desirable for the set point of the system to be within the supra comfort threshold region 1640.

As described above, the feedback controller 1530 increases or decreases the stimulus current to move the set point of the system along the profile 1602 to a target value. The set point of the system is the point along a profile of the measured response signal corresponding to the stimulus current and the value of the measured response signal, at a point in time. The feedback controller 1530 increases the stimulus current in accordance with a gain rate K₁, and the feedback controller 1530 decreases the stimulus current in accordance with a loss rate K₂. The loss K₂ rate may be equal to the negative of the gain rate K₁, or the loss rate K₂ may differ in magnitude from the gain rate K₁.

FIG. 17—Adjusting Gain Dependent on Set Point

FIG. 17 illustrates the profile 1602, of FIG. 16 , when the system is at a set point 1714 along the profile 1602, according to an embodiment. The system being at set point 1714 means that the value of the measured response signal is at level 1716 and the stimulus current at the previous stimulus clock cycle was at level 1712.

The gradient of the supra-threshold region 1710 is steeper than the gradient of the sub-threshold region 1708. Accordingly, applying the gain rate K₁ (or loss rate K₂) to the stimulus current when the set point of the system is in the sub-threshold region 1708 will result in a smaller change in the value of the measured response signal compared to the change in the value of the measured response signal if the same gain rate K₁ (or loss rate K₂) was applied when the system was in a set point in the supra-threshold region 1710.

Accordingly, in some embodiments, it is advantageous for the feedback controller to adjust the gain rate K₁ depending upon whether the set point of the system is in the sub-threshold or supra-threshold region of the profile of the measured (or adjusted) response signal. Furthermore, the feedback controller can adjust the gain rate K₁ based on the gradient of the region of the profile in which the set point of the system lies.

Similarly, in embodiments in which the feedback controller adjusts the stimulus current according to a loss rate K₂ that is not merely a negation of the gain rate K₁, it is advantageous for the feedback controller to adjust the loss rate K₂ depending upon whether the set point of the system is in the sub-threshold or supra-threshold region of the ECAP profile of the measured (or adjusted) response signal. Furthermore, the feedback controller can adjust the loss rate K₂ based on the gradient of the region of the ECAP profile in which the set point of the system lies.

In the embodiment illustrated in FIG. 17 , the target value 1718 is in the sub-threshold region 1708 of the profile 1602, and the set point 1714 of the system is in the supra perception threshold region of the profile 1602. The set point 1714 of the system is below the comfort threshold, above which the patient experiences uncomfortable or painful stimulation.

The feedback controller will reduce the stimulus current at a loss rate K₂, to reduce the value of the measured response signal. Once the set point of the system falls into the sub-threshold region 1708 of the profile 1602, if the feedback controller continues to decrease the stimulus current at the same loss rate K₂, the value may fall too far below the target value, due to the steeper gradient of the profile in the supra-threshold region.

Accordingly, once the set point of the system falls into the sub-threshold region of the profile 1602, the feedback controller adjusts the loss rate K₂ to ensure changes in the stimulus current result in small changes to the value of the measured response, so that the system can stabilise around the target value within the sub-threshold region.

In one embodiment, the feedback controller determines whether the set point of the system falls in the sub-threshold region 1708, the supra ECAP threshold region 1720, the supra perception threshold region 1730 or the supra comfort threshold region 1740. In one embodiment, the feedback controller adjusts the gain rate K₁ depending upon which of the three regions the set point of the system falls in. In some embodiments, the feedback controller adjusts the gain rate K₁ depending upon which of the three regions the set point of the system falls in, and the region that the target value is in. In one embodiment, the feedback controller adjusts the loss rate K₂ depending upon which of the three regions the set point of the system falls in. In one embodiment, the feedback controller adjusts the loss rate K₂ depending upon which of the three regions the set point of the system falls in, and which of the three regions the target value is in. In one embodiment, in response to the feedback controller determining that the set point of the system is in the same region as the target value, the feedback controller reduces the gain rate K₁ and loss rate K₂, so that the feedback controller adjusts the stimulus current in small increments with the aim of adjusting the set point of the system to be at the target value. In one embodiment, in response to the feedback controller determining that the set point of the system is in the supra comfort threshold region, the feedback controller increases the loss rate K₂, so that the feedback controller lowers stimulus current in large increments to reduce the value of the adjusted measured response, d′, quickly below the comfort threshold.

Depending upon a patient's sensitivity and preferences, the target value may be above or below the perception threshold. In one embodiment, in response to the target value being in the sub-perception threshold region, and the set point of the system being in the supra perception threshold region, the feedback controller increases the loss rate K₂, so that the set point of the system quickly drops down towards the target value.

In one embodiment, the feedback controller determines the location of the set point of the system relative to the sub-threshold or supra-threshold regions, (or relative to the supra ECAP threshold region, or supra perception threshold region, if applicable) of the profile. The feedback controller determines the location of the set point of the system by determining whether the value of the adjusted measured response signal, ′d, is greater than or less than the ECAP threshold (and greater than or less than the perception threshold, if applicable). Accordingly, the feedback controller receives and considers the value of the adjusted measured response signal, d′, from the detector, and compares this value to the ECAP threshold (and the perception threshold, if applicable).

The feedback controller configures the gain and loss rates based on whether the set point of the system is in the sub-threshold or supra-threshold region. As noted above, in some embodiments, the feedback controller considers the supra-threshold region to comprise a supra ECAP threshold region, or supra perception threshold region. In one embodiment, the feedback controller configures the gain and loss rates based on which region the set point of the system is in and which region the target value is in.

In one embodiment, the feedback controller receives a clinical setting parameter, from the clinical settings input 602, which indicates the gain and loss rates for each of the regions of the profile.

Gain Dependent on Location of Target

In some embodiments, it is advantageous to configure the gain rate K₁ and loss rate K₂ of the feedback controller based on whether the target value is in the sub-threshold or supra-threshold region.

In some embodiments, it is advantageous to configure the gain rate K₁ and loss rate K₂ of the feedback controller based on whether the set point of the system is in the same region as the target value, and whether the set point of the system is in the sub-threshold or supra-threshold region.

In one embodiment, if the target value is in the sub-threshold region, and the set point is also in the sub-threshold region, the feedback controller applies a gain or loss rate tailored for the sub-threshold region. However, if the target value is in the sub-threshold region, but the set point is in the supra-threshold region, the feedback controller applies a loss rate that will quickly reduce the set point of the system down to the sub-threshold region.

In one embodiment, if the target value is in the supra-threshold region, and the set point is also in the supra-threshold region, the feedback controller applies a gain or loss rate tailored for the supra-threshold region. However, if the target value is in the supra-threshold region, but the set point is in the sub-threshold region, the feedback controller applies a gain rate that will quickly increase the set point of the system up to the supra-threshold region.

In one embodiment, a patient, or clinician, sets a target value in either the sub-threshold or the supra-threshold region of a profile. In one embodiment, the feedback controller selects the sub-threshold gain rate and loss rate such that the sub-threshold region is always stable, assuming that the target will always be sub-threshold.

In an embodiment in which the target value is in the sub-threshold region, the feedback controller sets the loss rate for the supra-threshold region such that, if the value of the measured response occurs in the supra-threshold region, the feedback controller applies the loss rate to significantly reduce the stimulus current (e.g. half the stimulus current) so that the value of the measured response quickly returns to the sub-threshold region.

In one embodiment, the feedback controller uses the output of the detector (measured response, d) to determine a gain value for the feedback loop. If the system is at a set point below the ECAP threshold, the measured response, d, will not comprise an ECAP component. Accordingly, if the measured response, d, is non-zero, the measured response comprises an artefact component. The feedback controller adjusts the gain K1 according to the slope in the sub-ECAP threshold region. If the system is at a set point above the ECAP threshold, then the detector detects ECAPs and the feedback controller adjusts the gain based on the slope of the supra ECAP threshold region. In one embodiment, the target value may be in the supra ECAP threshold region, and can be below or above the perception threshold of the patient.

FIG. 18—Adjusting Forward Adjustment Function to Adjust Gradient of Profile

FIG. 18 is a graph illustrating a piecewise linear approximation of three example ECAP profiles 1802, 1812 and 1814 for a measured response signal, d, according to an embodiment. Profile 1802 is an example profile without the addition of a forward adjustment function. Profile 1812 comprises profile 1802 combined with forward adjustment function 1806. Profile 1814 comprises profile 1802 combined with forward adjustment function 1808.

Forward adjustment function 1808 has a steeper gradient compared to forward adjustment function 1806. Gradient is a function of the change in ECAP, as represented on the y-axis, for a set change in stimulus current, as represented on the x-axis.

The forward adjustment function 1806 increases the gradient of both the sub-threshold and supra-threshold regions of profile 1802 to produce profile 1812. To a greater extent, the forward adjustment function 1808 increases the gradient of both the sub-threshold and supra-threshold regions of profile 1802 to produce profile 1814.

The difference in gradient between the sub-threshold and supra-threshold regions of a profile can be represented by the angle between the sub-threshold and supra-threshold regions, as exemplified by angle 1816 for profile 1814. The size of the angle is inversely proportional to the difference in gradient between the sub-threshold and supra-threshold regions of a profile. Accordingly, a larger angle is indicatively of the sub-threshold and supra-threshold regions having a more similar gradient.

Reducing the difference in gradient of the sub-threshold region compared to the supra-threshold region means that there is less of a difference in the profile of the response as the set point of the system transitions between the sub-threshold region and the supra-threshold region, or vice versa.

In some embodiments, it is advantageous to select the gradient of the forward adjustment function to minimise the difference in the gradient between the sub-threshold and supra-threshold regions of the profile, and hence reduce the impact on loop dynamics.

The gradient of the forward adjustment function can be set according to a forward adjustment constant, c. The feedback controller selects a forward adjustment constant, c, for the forward adjustment function to provide a shifted profile that has a sub-threshold gradient that is greater than a minimum gradient value (e.g. 20 μV/mA) and a supra-threshold gradient that is less than a maximum gradient value (e.g. 500 μV/mA).

Determining the Activation Profile

During configuration of the neural stimulation device to suit a patient, a clinician performs a procedure to measure the sensitivity of the patient to the stimulation provided by the device. In one embodiment, the clinician configures the neural stimulation device to provide stimulation at a plurality of different stimulus currents. The clinician then notes the measured response of the patient in response to each of the plurality of different stimulus currents, to determine an activation profile of the measured response signal for that patient. During configuration of the neural stimulation device, the clinician also notes the ECAP threshold point, as being the stimulus current level at which an value is measurable (non-zero) by the detector.

In one embodiment, the gradient of the sub-threshold region of the activation profile and the gradient of the supra-threshold region are stored in the clinical settings, or in a memory component of the feedback controller.

Methods Performed by the Feedback Controller

FIG. 19 illustrates a method 1900 of controlling a neural stimulus as described with reference to FIGS. 5 and 6 , according to an embodiment. The neural stimulus is defined by at least one stimulus intensity parameter. The method is performed by the feedback controller 630 in that the feedback controller 630 generates 1902 a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue. Feedback controller 630 then measures 1904 a response of the tissue, evoked by the stimulus current. As explained above, the feedback controller 630 further determines 1906 a forward adjustment parameter as a function of the stimulus intensity parameter in order to increase the signal level above the noise level. Further, the feedback controller 630 determines 1908 a feedback parameter derived from the measured response and the forward adjustment parameter. Finally, the feedback controller 630 adjusts 1910 the stimulus intensity parameter according to the feedback parameter.

FIG. 20 illustrates a method 2000 of controlling a neural stimulus as described with reference to FIGS. 10 and 11 , according to an embodiment. The neural stimulus is defined by at least one stimulus intensity parameter. The method is performed by the feedback controller 1130 in that the feedback controller 1130 generates 2002 a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue. The feedback controller 1130 then measures 2004 a response of the tissue, evoked by the stimulus current. As explained above, the feedback controller 1130 further determines 2006 an artefact compensation component as a function of the stimulus intensity parameter and indicative of an artefact component of the measured response. Finally, the feedback controller 1130 adjusts 2008 the stimulus intensity parameter according to a feedback parameter derived from the measured response and the artefact compensation component.

FIG. 21 illustrates a method 2100 of controlling a neural stimulus as described with reference to FIGS. 12 and 13 , according to an embodiment. The neural stimulus is defined by at least one stimulus intensity parameter. The method is performed by the feedback controller 1330 in that the feedback controller 1330 generates 2102 a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue. The feedback controller 1330 then measures 2004 a response of the tissue, evoked by the stimulus current. As explained above, in response to the measured response being greater than a target value 2106, the feedback controller 1330 reduces 2108 the stimulus intensity parameter in accordance with a reduction rate. Further, in response to the measured response being less than a target value, the feedback controller 1330 increases 2110 the stimulus intensity parameter in accordance with a growth rate. A magnitude of the reduction rate is not equal to a magnitude of the growth rate.

FIG. 22 illustrates a method 2200 of controlling a neural stimulus as described with reference to FIGS. 15, 16, 17 and 18 , according to an embodiment. The neural stimulus is defined by at least one stimulus intensity parameter. The method is performed by the feedback controller 1530 in that the feedback controller 1530 generates 2202 a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue. The feedback controller 1530 then measures 2204 a response of the tissue, evoked by the stimulus current and associated with a threshold above which the response is measured reliably. As explained above, the feedback controller 1530 further determines 2206 a position of the set point of the measured response relative to the threshold. Finally, the feedback controller 1530 adjusts 2208 the stimulus intensity parameter according to a feedback parameter derived from the measured response and the position of the set point relative to the threshold.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

EXAMPLES OF THE INVENTION

Example 1. A method of controlling a neural stimulus, the neural stimulus being defined by at least one stimulus intensity parameter, the method comprising:

-   -   generating a stimulus intensity parameter to control a         stimulator that generates a stimulus current for application to         a tissue;     -   measuring a response of the tissue, evoked by the stimulus         current;     -   determining an artefact compensation component as a function of         the stimulus intensity parameter and indicative of an artefact         component of the measured response; and     -   adjusting the stimulus intensity parameter according to a         feedback parameter derived from the measured response and the         artefact compensation component.

Example 2. The method of Example 1, further comprising adjusting the measured response based on the artefact compensation component, to produce an adjusted measured response, and

wherein adjusting the stimulus intensity parameter comprises adjusting the stimulus intensity parameter according to a feedback parameter derived from the adjusted measured response and the artefact compensation component.

Example 3. A method of controlling a neural stimulus, the neural stimulus being defined by at least one stimulus intensity parameter, the method comprising:

-   -   generating a stimulus intensity parameter to control a         stimulator that generates a stimulus current for application to         a tissue;     -   measuring a response of the tissue evoked by the stimulus         current;     -   in response to the measured response being greater than a target         value, reducing the stimulus intensity parameter in accordance         with a reduction rate; and     -   in response to the measured response being less than the target         value, increasing the stimulus intensity parameter in accordance         with a growth rate,     -   wherein a magnitude of the reduction rate is not equal to a         magnitude of the growth rate.

Example 4. The method of Example 3, further comprising determining the reduction rate based on a duration of time for which the measured response is greater than the target value. 

1. A method of controlling a neural stimulus, the neural stimulus being defined by at least one stimulus intensity parameter, the method comprising: generating a stimulus intensity parameter to control a stimulator that generates a stimulus current for application to a tissue; measuring a response of the tissue, evoked by the stimulus current; determining a forward adjustment parameter as a function of the stimulus intensity parameter; determining a feedback parameter derived from the measured response and the forward adjustment parameter; and adjusting the stimulus intensity parameter according to the feedback parameter.
 2. The method of claim 1, wherein the forward adjustment parameter is non-zero when the stimulus intensity parameter is non-zero.
 3. The method of claim 1, further comprising providing a target response level, wherein determining a feedback parameter comprises: adjusting the target response level in accordance with the forward adjustment parameter to produce an adjusted target response level; and deriving the feedback parameter from a difference between the measured response and the adjusted target response level.
 4. The method of claim 1, wherein determining a feedback parameter comprises adjusting the measured response according to the forward adjustment parameter to produce an adjusted response.
 5. The method of claim 1, wherein the function of the stimulus intensity parameter is a forward adjustment function, wherein the forward adjustment function defines a monotonically increasing relationship between the forward adjustment parameter and the stimulus intensity parameter.
 6. The method of claim 1, further comprising: determining a change in an impedance level of the tissue; and adjusting a gradient of the forward adjustment function based on the change the impedance level.
 7. The method of claim 6, wherein adjusting the gradient of the forward adjustment function comprises: in response to an increase in the impedance level, reducing the gradient of the forward adjustment function; and in response to a decrease in the impedance level, increasing the gradient of the forward adjustment function.
 8. The method of claim 4, wherein the feedback parameter is derived according to the difference between a target stimulus intensity level and the adjusted response.
 9. The method of claim 8, further comprising determining an adjusted target stimulus intensity level based on the target stimulus intensity level and the forward adjustment function.
 10. The method of claim 9, further comprising adjusting the forward adjustment function to increase a difference between the adjusted target stimulus intensity level and a comfort stimulus intensity threshold.
 11. The method of claim 1, further comprising: determining an artefact compensation component based on an artefact component of the measured response of the tissue; and adjusting the measured response based on the artefact compensation component.
 12. The method of claim 11, further comprising determining the artefact component as a function of the stimulus intensity parameter.
 13. The method of claim 11, wherein adjusting the measured response based on the artefact compensation component comprises adjusting the forward adjustment parameter based on the artefact compensation component.
 14. The method of claim 1, wherein adjusting the stimulus intensity parameter according to the feedback parameter derived from the measured response comprises: in response to the measured response being greater than a target value, reducing the stimulus intensity parameter in accordance with a reduction rate; and in response to the measured response being less than the target value, increasing the stimulus intensity parameter in accordance with a growth rate, wherein a magnitude of the reduction rate is not equal to a magnitude of the growth rate.
 15. An implantable device for controllably applying a neural stimulus defined by at least one stimulus intensity parameter, the device comprising: one or more stimulus electrodes to deliver stimulus to a tissue to evoke a compound action potential response of the tissue; a stimulator for controlling the one or more stimulus electrodes in accordance with the at least one stimulus intensity parameter; measurement circuitry for measuring the evoked compound action potential response of the tissue; and a control unit configured to, generate the stimulus intensity parameter, measure the response of the tissue, evoked by the stimulus current, determine a forward adjustment parameter as a function of the stimulus intensity parameter, determine a feedback parameter derived from the measured response and the forward adjustment parameter, and adjust the stimulus intensity parameter according to the feedback parameter. 16-25. (canceled)
 26. The device of claim 15, wherein the control unit is configured to determine the feedback parameter by: adjusting a target response level in accordance with the forward adjustment parameter to produce an adjusted target response level; and deriving the feedback parameter from a difference between the measured response and the adjusted target response level.
 27. The device of claim 15, wherein the control unit is configured to determine the feedback parameter by adjusting the measured response according to the forward adjustment parameter to produce an adjusted response.
 28. The device of claim 15, wherein the function of the stimulus intensity parameter is a forward adjustment function, wherein the forward adjustment function defines a monotonically increasing relationship between the forward adjustment parameter and the stimulus intensity parameter.
 29. The device of claim 15, wherein the control unit is further configured to: determine an artefact compensation component based on an artefact component of the measured response of the tissue; and adjust the measured response based on the artefact compensation component.
 30. The device of claim 15, wherein the control unit is configured to adjust the stimulus intensity parameter according to the feedback parameter derived from the measured response by: in response to the measured response being greater than a target value, reducing the stimulus intensity parameter in accordance with a reduction rate; and in response to the measured response being less than the target value, increasing the stimulus intensity parameter in accordance with a growth rate, wherein a magnitude of the reduction rate is not equal to a magnitude of the growth rate. 